Rispolept of Konsta - instructions for use, doses, side effects, contraindications

Solvent: carmellose sodium 40 mPa * s - 22.5 mg, polysorbate 20 - 1.0 mg, sodium hydrogen phosphate dihydrate - 1.27 mg, citric acid anhydrous - 1.0 mg, sodium chloride - 6.0 mg, sodium hydroxide - 0 , 54 mg, water for injection - up to 1 ml.

Description:

Powder: white or almost white powder, free from visible foreign impurities.

Solvent: transparent clear solution free from visible mechanical inclusions.

Suspension: the preparation should easily form a suspension in the solvent, the slurry should not have lumps or visible inclusions. Suspension must pass through the needle smoothly, with little resistance or no resistance.

Pharmacotherapeutic group:antipsychotic agent (antipsychotic)

ATX: & nbsp

N.05.A.X Other antipsychotics

N.05.A.X.08 Risperidone

Pharmacodynamics:

Risperidone is an selective monoaminergic antagonist. It has a high affinity for serotonergic 5-HT₂receptors and dopaminergic D₂receptors. Besides, risperidone binds to alpha₁-adrenergic receptors and, to a lesser extent, with H₁-gistaminergic and alpha₂-adrenergic receptors. Risperidone does not bind to cholinergic receptors. Although risperidone is a potent antagonist D₂-receptors, due to which it improves the positive symptoms of schizophrenia, this drug,in comparison with typical neuroleptics, to a lesser extent inhibits motor activity and less often causes catalepsy. Thanks to a balanced central antagonism for serotonin and dopamine receptors risperidone rarely causes extrapyramidal side effects and has a therapeutic effect on the negative and affective symptoms of schizophrenia.

Pharmacokinetics:

Risperidone is metabolized by isoenzyme CYP2D6 to 9-hydroxyrisperidone, which has the same pharmacological activity as itself risperidone. Risperidone and 9-hydroxyrisperidone form an active antipsychotic fraction. Another way of metabolizing risperidone is N-dealkylation.

In fast metabolizers, the clearance of active antipsychotic fraction and risperidone is 5.0 and 13.7 l / h, respectively, and in weak metabolizers - 3.2 and 3.3 l / h, respectively.

General characteristics of risperidone after injection of Rispolept Konsta®

With a single intramuscular injection of the preparation, Rispeplet Konsta®, the risperidone release profile consists of a small initial phase (<1% dose), followed by an interval of 3 weeks.After intramuscular injection, the main release of risperidone begins in 3 weeks, is maintained from the 4th to the 6th week, and decreases by the 7th week. In this regard, the patient should take an additional antipsychotic drug within the first 3 weeks after the start of treatment with the drug Rispolept Konsta®.

The combination of the release profile of risperidone and the dosing regimen (intramuscular injection every two weeks) ensures the maintenance of plasma concentrations of risperidone in the plasma. Therapeutic concentrations persist until the 4th-6th week after the last injection of Rispolept® Consta®. The elimination phase is completed approximately 7-8 weeks after the last injection.

Risperidone is completely absorbed from the suspension of Rispolept Konsta®.

Risperidone is rapidly distributed in the tissues of the body. The volume of distribution is 1-2 l / kg. In the plasma risperidone binds to albumin and alpha₁acid glycoprotein. The connection with the plasma proteins of risperidone is 90%, and 9-hydroxyrisperidone - 77%.

After intramuscular injections of Rispolept® Constan® in doses of 25 or 50 mg once every two weeks, mean valuesthe minimum and maximum plasma concentrations of the active antipsychotic fraction are 9.9-19.2 ng / ml and 17.9-45.5 ng / ml, respectively. In this dosage regimen, the pharmacokinetics of risperidone are linear. In long-term use (12 months) in patients who once every two weeks were injected with the preparation Rispolept Konsta® in doses of 25-50 mg, no cisulation of risperidone was observed. The study of single dose application of the oral form of risperidone showed higher plasma concentrations and reduced clearance of the active antipsychotic fraction by 30% in elderly patients and by 60% in patients with renal insufficiency. The concentrations of risperidone in plasma in patients with hepatic insufficiency were normal, but the mean free plasma fraction increased by 35%.

Indications:

Treatment and prevention of exacerbations of schizophrenia and schizoaffective disorders.

Contraindications:

- Hypersensitivity to risperidone or any other ingredient of this drug;

- lactation period;

- Children under 18 years.

Carefully:

Use with caution under the following conditions:

- diseases of the cardiovascular system (chronic heart failure, suffered myocardial infarction, conduction disorders of the heart muscle);

- dehydration and hypovolemia;

- disorders of cerebral circulation;

- Parkinson's disease;

- convulsions and epilepsy (including in the anamnesis);

- severe renal or hepatic impairment (see section "Method of administration and dose");

- drug abuse or drug dependence;

- conditions predisposing to the development of tachycardia such as "pirouette" (bradycardia, electrolyte imbalance, concomitant medication prolonging the interval QT);

- brain tumor;

- intestinal obstruction, cases of acute drug overdose, Reye's syndrome (the antiemetic effect of risperidone may mask the symptoms of these conditions);

- pregnancy.

Pregnancy and lactation:

Application in pregnancy

There are no data on the safety of risperidone in pregnant women. In animal experiments risperidone did not have a direct toxic effect on the reproductive system, but caused some indirect effects mediated through prolactin and the central nervous system.None of the studies risperidone did not possess a teratogenic effect. In the case of a woman taking antipsychotics (including Rispolept®) in the third trimester of pregnancy, there is a risk of developing extrapyramidal disorders and / or withdrawal syndrome of varying severity in newborns. These symptoms may include agitation, hypertension, hypotension, tremor, drowsiness, respiratory disorders, and breast-feeding disorders.

The drug Rispolept® Constan® can be used during pregnancy only in those cases where the potential benefit for a woman outweighs the possible risk to the fetus.

Application in lactation

In animal experiments risperidone and 9-hydroxyrisperidone are excreted with milk. It was also found that risperidone and 9-hydroxyrisperidone are excreted with human milk. Therefore, women taking Rispolept® Constan® should not breast-feed.

Dosing and Administration:

In patients who have not previously received risperidone, it is recommended to determine the tolerability of oral dosage forms of risperidone before starting treatment with Rispolept Konsta®.

Rispeplet Konsta® is injected once every 2 weeks by deep injection into the gluteus or deltoid muscle using a sterile needle attached to the syringe. For injection into the deltoid muscle, a 25 mm needle is used, a 51 mm needle is used to inject into the gluteus muscle. Injections should be done alternately in the right and left gluteal or deltoid muscles. The drug can not be administered intravenously.

Instructions for use are given in the section "Instructions for use".

Adults (over 18 years)

The recommended dose is 25-50 mg intramuscularly once every 2 weeks. Transfer of patients receiving risperidone orally at a fixed dose for two weeks or more, the preparation Rispolept Konsta® is recommended according to the following scheme.

Patients receiving risperidone orally in a dose of 4 mg or less, should be transferred to the preparation Rispolept Konsta® at a dose of 25 mg. Patients receiving risperidone orally in a dose of more than 4 mg, should be transferred to the preparation Rispolept Konsta® at a dose of 37.5 mg.

In clinical studies, there was no increase in efficacy with 75 mg.The maximum dose should not exceed 50 mg once every 2 weeks. In the 3-week period after the first administration of Rispolept Konsta® and with exacerbation of schizophrenia, the patient should take an effective antipsychotic agent, (risperidone orally or previously used antipsychotic).

The dose of the drug can be increased no more than once every 4 weeks. The effect of such a dose increase should be expected not earlier than 3 weeks after the first injection of the increased dose.

Children (18 years and under)

Rispolept Konsta® has not been studied in children younger than 18 years.

Elderly patients (65 years and older)

The recommended dose is 25 mg intramuscularly once every 2 weeks. In the 3-week period after the first injection of Rispolept®, the patient should take an effective antipsychotic. Clinical data on the use of Rispolept Konsta® in elderly patients are limited, so use with caution in this patient category.

Patients with impaired hepatic or renal function

At present, there is no data on the use of Rispolept Konsta® in patients with impaired hepatic or renal function.

If necessary, drug therapy Rispolept Konsta® patients with impaired hepatic or renal function, in the first week is recommended to ingest 0.5 mg risperidone oral dosage form twice a day. During the second week, the patient may take 1 mg of risperidone twice daily or 2 mg of risperidone once a day. If the patient tolerates a good oral dose of at least 2 mg, then he can inject intramuscularly 25 mg of the drug Rispolept Konsta® once every 2 weeks.

Side effects:

The most frequent side effects (≥1 / 10) are: insomnia, anxiety, headache, upper respiratory system infections, parkinsonism, depression and akathisia.

In the postmarketing period of observation, serious reactions at the injection site were noted, including necrosis, abscess, inflammation of subcutaneous fat, ulceration, hematoma, cyst and nodular thickening. The frequency of occurrence of these reactions is unknown (it is impossible to estimate the frequency from the available data). In some cases, surgical intervention was required. The side effects of Rispolept Konsta®, which were observed during clinical trials and in the post-marketing period of follow-up, are given below.

The frequency of side effects was classified as follows: very frequent (≥1/10), frequent (≥1 / 100 and <1/10), infrequent (≥1 / 1000 and <1/100), rare (≥1 / 10000 and < 1/1000), very rare (<1/10000) and with unknown frequency (it is impossible to estimate the frequency from the available data).

In each frequency group, side effects are given in order of decreasing severity. Side effects are given with frequency distribution and system-standard classes.

Violations of laboratory and instrumental indicators:

often - ECG disorders, increased prolactin levels¹, an increase in the activity of microsomal liver enzymes, an increase in the activity of transaminases, an increase or decrease in body weight;

infrequently - interval lengthening QT on an electrocardiogram.

Disorders from the cardiovascular system:

often - atrioventricular block, tachycardia;

infrequently - blockade of the bundle of the Guiss, atrial fibrillation, bradycardia, sinus bradycardia, palpitation.

Hematologic disorders and disorders of the lymphatic system:

often - Anemia;

infrequently - Thrombocytopenia, neutropenia;

rarely - agranulocytosis.

Disturbances from the nervous system:

Often - Parkinsonism², akathisia², headache;

often - dizziness, sedation, drowsiness, tremor, dystonia², tardive dyskinesia, dyskinesia²;

infrequently - cramps, fainting, postural dizziness, hypoesthesia, paresthesia, lethargy, hypersomnia.

Disturbances on the part of the organ of sight:

often - blurred vision, conjunctivitis;

rarely - syndrome of flabby iris (intraoperative)⁴;

with unknown frequency - occlusion of the retina artery.

Violations from the organ of hearing and labyrinth:

often - vertigo;

infrequently - earache.

Respiratory, thoracic disorders and disorders of the mediastinum:

often - shortness of breath, cough, nasal congestion, pharyngolaryngeal pain;

rarely - sleep apnea syndrome.

Disorders from the gastrointestinal tract:

often - vomiting, diarrhea, constipation, nausea, abdominal pain, dyspepsia, toothache, dry mouth, stomach discomfort, gastritis;

rarely - mechanical intestinal obstruction, pancreatitis;

rarely - intestinal obstruction.

Disorders from the kidneys and urinary tract:

often - urinary incontinence;

infrequently - urinary retention.

Disturbances from the skin and subcutaneous tissues:

often - rash, eczema;

infrequently - Quincke's edema, itching, acne, alopecia, dry skin;

Disturbances from the musculoskeletal system and connective tissue:

often - arthralgia, back pain, pain in the extremities, myalgia;

infrequently - Muscular weakness, pain in the neck, pain in the buttocks, musculoskeletal pain in the chest.

Disorders from the endocrine system:

rarely - violation of secretion antidiuretic hormone.

Metabolic and nutritional disorders:

often - hyperglycemia;

infrequently - diabetes³, increased appetite, decreased appetite;

rarely - hypoglycemia;

rarely - diabetic ketoacidosis;

with unknown frequency - water intoxication.

Infections:

Often - infections of the upper respiratory tract;

often - pneumonia, influenza, lower respiratory tract infections, bronchitis, urinary tract infections, ear infections, sinusitis, viral infections;

infrequently - Cystitis, gastroenteritis, infections, localized infections, subcutaneous abscess.

Injuries, poisonings and complications associated with the procedure for administering the drug:

often - a fall;

infrequently - pain during the procedure of drug administration.

Vascular disorders:

often hypertension, hypotension;

infrequently - orthostatic hypotension.

General violations and violations in the field of drug administration:

often - Pyrexia, peripheral edema, chest pain, fatigue, pain, pain in the area of drug administration, asthenia, influenza-like condition;

infrequently - compaction in the area of drug administration, compaction, reactions in the area of drug administration, discomfort in the chest, sluggishness, poor health;

rarely hypothermia.

Immune system disorders:

infrequently hypersensitivity;

with unknown frequency anaphylactic reactions.

Hepatobiliary disorders:

rarely - jaundice.

Disorders from the reproductive system and mammary glands:

often - amenorrhea, erectile dysfunction, galactorrhea;

infrequently - sexual dysfunction, gynecomastia;

with unknown frequency - Priapism.

Mental disorders:

Often - Depression, insomnia, anxiety;

often - agitation, sleep disorders;

infrequently - mania, decreased libido, nervousness.

¹- giperprolaktinemiya in some cases can lead to gynecomastia, menstrual disorders, amenorrhea and galactorrhea.

²- extrapyramidal disorders may manifest as: Parkinsonism (hypersalivation, musculoskeletal stiffness, parkinsonism, drooling, rigidity as a "cogwheel", bradykinesia, hypokinesia, masculine face, muscle tension, akinesia, stiff neck, muscle stiffness, parkinsonic gait, violations of the glabellar reflex), akathisia (akathisia, restlessness, hyperkinesia and restless leg syndrome), tremor, dyskinesia (dyskinesia, muscle twitching, choreoathetosis, athetosis and myoclonus), dystonia. Dystonia includes dystonia, muscle spasms, hypertension, torticollis, involuntary muscle contractions, muscle contracture, blepharospasm, eyeball movements, paralysis of the tongue, facial spasm, laryngospasm, myotonia, opisthotonus, oropharyngeal spasm, pleurototonus, spasm of the tongue and trismus. Tremor includes tremor and Parkinson's tremor tremor. It should also be noted that there is a wider range of symptoms that do not always have extrapyramidal origin.

³- in placebo-controlled studies, diabetes was observed in 0.18% of patients taking risperidone compared with 0.11% of patients in the placebo group. The overall incidence of diabetes by the results of all clinical trials was 0.43% of all patients taking risperidone.

⁴ - was observed only in the postmarketing period.

The following side effects are further described in the clinical studies of oral dosage forms of risperidone, but not with the use of a prolonged injection of risperidone - Rispolept Konsta®. Side effects are given with the distribution of system-organ classes:

Violations of laboratory indicators: an increase in body temperature, an increase in the number of eosinophils, an increase in the number of leukocytes, a decrease in the level of hemoglobin, an increase in the level of creatine phosphokinase, a decrease in body temperature.

Infections: tonsillitis, inflammation of subcutaneous fat, otitis media, eye infections, acarobacteria, respiratory tract infections, onychomycosis, chronic otitis media.

From the side of the blood and lymphatic system: granulocytopenia.

From the immune system: hypersensitivity to the drug.

Metabolic and nutritional disorders: anorexia, polydipsia.

Mental disorders: confusion, lethargy, anorgasmia, affective flattening.

From the nervous system: absence of response to stimuli, loss of consciousness, malignant neuroleptic syndrome, diabetic coma, stroke, depression of consciousness, cerebral ischemia, cerebrovascular disorders, transient ischemic attack, dysarthria, attention disturbance, imbalance, speech impairment, impaired coordination, impaired movement.

Ophthalmic disorders: ocular hyperemia, discharge from the eyes, edema around the eyes, dry eyes, increased lacrimation, photophobia, decreased visual acuity, involuntary eyeball rotation, glaucoma.

From the side of the ear and the labyrinth: tinnitus.

Vascular disorders: tides.

Respiratory, thoracic and mediastinal disorders: wheezing, aspiration pneumonia, congestion in the lungs, respiratory failure, wheezing, epistaxis, nasal congestion, hyperventilation, dysphonia.

From the gastrointestinal tract: Dysphagia, fecal incontinence, fecaloma, edema of lips, cheilitis.

From the skin and subcutaneous tissues: skin lesions, skin disorders, skin discoloration, seborrheic dermatitis, hyperkeratosis, dandruff, erythema.

From the musculoskeletal system and connective tissue: rhabdomyolysis, swelling of the joints, impaired posture, stiffness in the joints.

From the side of the kidneys and urinary tract: enuresis, dysuria, pollakiuria.

On the part of the reproductive system and mammary glands: erectile dysfunction, vaginal discharge, menstruation disorder.

General disorders and phenomena caused by the administration of the drug: general edema, edema of the face, gait disturbance, thirst, chills, cold extremities, withdrawal syndrome.

Class Effects

As with the use of other antipsychotics, very rare cases of lengthening the interval QT were observed in the post-marketing period of observation. Other class effects from the cardiovascular system, observed with the use of antipsychotics, which extend the interval QT, include: ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia, sudden death, cardiac arrest and bidirectional ventricular tachycardia.

Venous thromboembolism

Cases of venous thromboembolism, including pulmonary embolism and cases of deep vein thrombosis, were observed with the use of antipsychotics (the frequency is unknown).

Weight gain

In a 12-week, placebo-controlled study, 9% of patients taking Rispolept® Constan® received an increase in body weight of at least 7% compared to 6% of patients taking placebo at the time of completion of the study. In another clinical study, lasting 1 year, changes in body weight for individual patients were ± 7% of the mean; In 25% of patients, an increase in body weight of at least 7% was observed.

Overdose:

When using parenteral dosage forms of risperidone, an overdose is less likely than with the use of oral forms (film-coated tablets and oral solution), and therefore information on oral forms.

Symptoms:

Symptoms observed in overdose are enhanced known pharmacological effects. These include sedation, drowsiness, tachycardia, lowering blood pressure, and extrapyramidal disorders. The lengthening of the interval QT and convulsions.Bi-directional ventricular tachycardia was noted with simultaneous administration of an increased dose of oral risperidone and paroxetine.

In case of an overdose, the possibility of involving several drugs should be considered.

Treatment:

Provide and maintain airway patency, adequate oxygenation and ventilation. It is necessary to monitor the function of the cardiovascular system, which should include constant ECG monitoring to identify possible arrhythmias.

Rispolept® does not have a specific antidote, and therefore treatment should be aimed at maintaining the function of the central nervous system and the cardiovascular system, and detoxification therapy should also be carried out. With severe extrapyramidal symptoms, anticholinergic drugs should be administered. Medical surveillance and monitoring should continue until the signs of an overdose disappear.

Interaction:

The interactions of Rispolept Konsta® with other drugs have not been evaluated systematically. The data on interactions presented in this section are based on studies of the oral form of Rispolept®.

Interactions associated with the pharmacodynamics of the drug

Drugs of central action and alcohol

Rispolept Konsta® increases the severity of oppressive effects on the CNS of opioid analgesics, hypnotics, anxiolytics, tricyclic antidepressants, agents for general anesthesia, alcohol.

Levodopa and dopamine receptor agonists

Rispolept Konsta® can weaken the action of levodopa and other dopamine receptor agonists. If simultaneous use is required, especially in patients with terminal stage of Parkinson's disease, the minimum effective doses of each drug should be given.

Drugs with hypotensive effect

Clinically significant arterial hypotension is observed with the combined use of risperidone with antihypertensive agents.

Drugs that increase interval QT

Caution should be exercised when using the drug Rispolept Konsta® with medications that increase the interval QT, such as antiarrhythmics (quinidine, disopyramide, procainamide, propafenone, amiodarone, sotalol), tricyclic antidepressants (amitriptyline), tetracyclic antidepressants (maprotiline), some antihistamines, other antipsychotics, some antimalarial drugs (quinine, mefloquine), drugs that cause electrolyte imbalance (hypokalemia, hypomagnesemia), bradycardia and drugs that inhibit the metabolism of risperidone in the liver.

Paliperidone

Because the paliperidone is an active metabolite of risperidone, caution should be exercised with the simultaneous use over a long period of the drug XEPLION and risperidone or paliperidone orally. Data on the safety of the use of the drug KSEPLION and other antipsychotics are limited.

Interactions associated with the pharmacokinetics of the drug

Risperidone in mainly metabolized by the isoenzyme CYP2D6 and to a lesser extent CYP3A4. how risperidone, and its active metabolite 9-hydroxyrisperidone, are substrates of P-glycoprotein (P-GP).

Substances that alter the activity of CYP2D6, or substances strongly inhibiting or inducing activity CYP3A4 and / or P-GP, may influence the pharmacokinetics of risperidone and the active antipsychotic fraction.

Strong inhibitors CYP2D6

Joint use of Rispolept ® Constan® with strong inhibitor CYP2D6 can increase the concentration of risperidone in plasma, but to a lesser extent, the active antipsychotic fraction. Higher doses of a strong inhibitor CYP2D6 can increase the concentration of risperidone and the active antipsychotic fraction (eg, paroxetine, see below). It is expected that other inhibitors of CYP2D6, such as quinidine, can affect the concentration of risperidone in plasma in a similar way. If paroxetine, quinidine or another strong CYP2D6 inhibitor is used concomitantly, especially at higher doses, the dose of Rispolept® Constan® should be adjusted.

Inhibitors CYP3A4 and / or P-GP

Co-administration of Rispolept® Constan® with a strong inhibitor CYP3A4 and / or P-GP can significantly increase plasma concentrations of risperidone and an active antipsychotic fraction. With the simultaneous use of itraconazole or another strong inhibitor CYP3A4 and / or P-GP, the dose of Rispolept Konsta® should be adjusted.

Inductors CYP3A4 and / or P-GP

Joint use of the preparation Rispolept Konsta® with a strong inducer CYP3A4 and / or P-GP can reduce the plasma concentration of risperidone and the active antipsychotic fraction. When carbamazepine or another strong inducer CYP3A4 and / or P-GP is used concomitantly, the dose of Rispolept Konsta® should be adjusted.

The degree of induction can vary in time with the achievement of maximum effect up to 2 weeks after administration and a decrease in induction up to 2 weeks after drug withdrawal.

Preparations that bind strongly to plasma proteins

When combined with drugs that have a high binding to plasma proteins, there is no clinically significant displacement of the drug from plasma proteins.

At simultaneous application it is necessary to address to the instruction on application of a corresponding medical preparation and if necessary to correct doses of accepted preparations.

Antibacterial drugs

- Erythromycin, a moderate inhibitor CYP3A4 and the P-GP, does not alter the pharmacokinetics of risperidone and the active antipsychotic fraction.

- Rifampicin, strong inducer CYP3A4 and P-GP, reduces the concentration in the plasma of the active antipsychotic fraction.

Anticholinesterase drugs

- Donepezil and galantamine, substrates CYP2D6 and CYP3A4, do not have a clinically significant effect on the pharmacokinetics of risperidone and the active antipsychotic fraction.

Antiepileptic drugs

- Carbamazepine, a strong inducer CYP3A4 and P-GP, reduces the plasma content of the active antipsychotic fraction of risperidone. A similar effect is observed with the use of phenytoin and phenobarbital, which are also inducers of CYP3A4 and P-GP.

- Topiramate moderately reduces the bioavailability of risperidone, but not the active antipsychotic fraction. This interaction is not considered clinically significant.

- Risperidone does not have a clinically significant effect on the pharmacokinetics of valproic acid or topiramate.

Antifungal drugs

- Itraconazole, a strong inhibitor CYP3A4 and P-GP, at a dose of 200 mg / day, increases the plasma concentration of the active antipsychotic fraction by approximately 70% with risperidone at a dose of 2 to 8 mg / day.

- Ketoconazole, a strong inhibitor CYP3A4 and P-GP, in a dose of 200 mg / day increases the concentration of risperidone in plasma and reduces the concentration of 9-hydroxyrisperidone in plasma.

Antipsychotics

- Phenothiazines can increase the concentration of risperidone in plasma, but to a lesser extent the concentration of the active antipsychotic fraction.

- Aripiprazole, substrate CYP2D6 and CYP3A4: risperidone does not affect the pharmacokinetics of aripiprazole and its active metabolite, dihydroaripiprazole.

Antiviral drugs

- Inhibitors of protease: official research data are not available. As ritonavir is a potent inhibitor of CYP3A4 and a weak inhibitor of CYP2D6, ritonavir and protease inhibitors, ritonavir-enhanced, may lead to an increase in the concentration of risperidone and the active antipsychotic fraction.

Beta-blockers

- Some beta-blockers may increase the concentration of risperidone in plasma, but not the active antipsychotic fraction.

Blocks of "slow" calcium channels

- Verapamil, a moderate inhibitor CYP3A4 and P-GP, increases the concentration of risperidone and the active antipsychotic fraction in plasma.

Cardiac glycosides

- Risperidone does not have a clinically significant effect on the pharmacokinetics of digoxin.

Diuretics

- See "Specific guidance" on the increased mortality of elderly patients with dementia in the combined use of furosemide and oral forms of risperidone.

Gastrointestinal drugs

- Antagonists of H₂-receptors: cimetidine and ranitidine which are weak inhibitors CYP2D6 and CYP3A4, increase the bioavailability of risperidone, but have a minimal effect on the concentration of the active antipsychotic fraction.

Lithium preparations

- Risperidone does not have a clinically significant effect on the pharmacokinetics of lithium preparations.

Serotonin reuptake inhibitors and tricyclic antidepressants

- Fluoxetine, a strong inhibitor CYP2D6, increases the concentration of risperidone in plasma, but to a lesser extent affects the concentration of the active antipsychotic fraction.

- Paroxetine, a strong inhibitor CYP2D6, increases the concentration of risperidone in plasma, but at doses up to 20 mg / day to a lesser extent affects the concentration of the active antipsychotic fraction.

However, higher doses of paroxetine may increase the concentration of the active antipsychotic fraction of risperidone.

- Tricyclic antidepressants may increase the concentration of risperidone in plasma, but do not affect the concentration of the active antipsychotic fraction.

Amitriptyline does not affect the pharmacokinetics of risperidone or the active antipsychotic fraction.

- Sertraline, is a weak inhibitor CYP2D6, a fluvoxamine - a weak inhibitor CYP3A4. In doses up to 100 mg / day sertraline and fluvoxamine have no clinically significant effect on the concentration of the active antipsychotic fraction of risperidone. However, the use of doses above 100 mg / day can lead to an increase in the concentration of risperidone and the active antipsychotic fraction.

Special instructions:

In patients who have not previously received risperidone, it is recommended to determine the tolerability of oral dosage forms of risperidone before starting treatment with Rispolept Konsta®.

Use in elderly patients with dementia

The use of Rispolept® Konsta® has not been studied in elderly patients with dementia, as it is not indicated for this group of patients. The drug Rispolept® Constan® is not intended to treat behavioral disorders associated with dementia.

Increased mortality in elderly patients with dementia

In elderly patients with dementia in the treatment of atypical antipsychotic agents, there was an increased mortality compared to the placebo group in the meta-analysis of 17 controlled trials of atypical antipsychotics, including oral risperidone. In placebo-controlled trials of oral risperidone for this population, the rate of death was 4.0% for patients taking risperidone, compared with 3.1% for the placebo group. The average age of the deceased patients is 86 years (range 67-100 years). The data collected from two extensive observational studies show that elderly patients with dementia who are treated with typical antipsychotics also have a slightly increased risk of death compared to patients who do not receive treatment. At the moment, there is insufficient data to accurately assess this risk. The cause of this risk increase is also unknown. Also, the extent to which an increase in mortality may not be applicable to antipsychotics, nor to the characteristics of this group of patients, has been determined.

Simultaneous application with furosemide

In elderly patients with dementia, there was an increased mortality with simultaneous furosemide and risperidone taken orally (7.3%, mean age 89 years, range 75-97 years) compared with the group taking only risperidone (3.1%, average age 84 years, range 70-96 years) and a group that only took furosemide (4.1%, average age 80 years, range 67-90 years). Increased mortality of patients taking risperidone together with furosemide, was observed during 2 out of 4 clinical trials. Joint use of risperidone with other diuretics (mainly with thiazide diuretics in small doses) was not accompanied by an increase in mortality.

There are no pathophysiological mechanisms that explain this observation. Nevertheless, special care should be taken when prescribing the drug in such cases. Before appointment, the risk / benefit ratio must be carefully assessed. There was no increase in mortality in patients taking other diuretics simultaneously with risperidone. Regardless of treatment, dehydration is a common risk factor for mortality and should be carefully monitored in elderly patients with dementia.

Undesirable effects from the cerebrovascular system

In placebo-controlled clinical trials in patients with dementia, taking some atypical antipsychotics, an increased risk of cerebrovascular adverse events was approximately 3-fold.Combined data from 6 placebo-controlled trials, including mainly elderly patients with dementia (age over 65 years), showed that cerebrovascular undesirable events (serious and non-serious) occurred in 3.3% (33/1009) of patients taking risperidone, and in 1.2% (8/712) of patients taking placebo. The risk ratio was 2.96 (1.34, 7.50) with a confidence interval of 95%. The mechanism of increasing the risk is unknown. Increased risk is not excluded for other antipsychotics, as well as for other patient populations. Rispolept Konsta® should be used with caution in patients with risk factors for stroke.

Orthostatic hypotension

Risperidone has alpha-adrenoblocking activity, and therefore can cause orthostatic hypotension, especially at the beginning of therapy. Clinically significant hypotension was observed in the postmarketing period when combined with antihypertensive drugs. Risperidone should be used with caution in patients with known cardiovascular diseases (eg, heart failure, myocardial infarction, conduction disorders, dehydration, hypovolemia or cerebrovascular disease).It is recommended that the benefit / risk ratio be evaluated carefully when assessing the possibility of continuing therapy with Rispolept Konsta®.

Violations from the blood (leukopenia, neutropenia and agranulocytosis)

It is reported cases of the occurrence of leukopenia, neutropenia and agranulocytosis with the use of antipsychotic drugs, including the preparation Rispolept Konsta®.

During post-registration observation, very rare cases of agranulocytosis (<1/10000 patients) are reported.

During the first few months of therapy, patients with a clinically significant decrease in the number of white blood cells or leukopenia or neutropenia caused by taking medications should be monitored in a history. Consideration should be given to the abolition of the Rispolept® Konsta® preparation with the first signs of a clinically significant reduction in the number of white blood cells in the absence of other causative factors.

Patients with clinically significant neutropenia should be carefully monitored for fever or other signs or symptoms of infection and should immediately begin treatment for these conditions.The use of Rispolept® Konsta® in patients with severe neutropenia should be discontinued (neutrophil count <1х10⁹/ l) and track the number of white blood cells before recovery.

Late dyskinesia and extrapyramidal disorders

Drugs that have the properties of dopamine receptor antagonists can cause tardive dyskinesia, which is characterized by rhythmic involuntary movements, predominantly of the tongue and / or facial musculature.

The occurrence of extrapyramidal symptoms is a risk factor for the development of tardive dyskinesia. If the patient has objective or subjective symptoms indicating late dyskinesia, it is necessary to consider the feasibility of the abolition of all antipsychotics.

Malignant neuroleptic syndrome (CNS)

Antipsychotic drugs, including risperidone, can cause malignant neuroleptic syndrome (CNS), which is characterized by hyperthermia, rigidity of muscles, instability of autonomic nervous system function, depression of consciousness, as well as increase in serum concentrations of creatine phosphokinase.In patients with ZNS, myoglobinuria (rhabdomyolysis) and acute renal failure may also occur. If a patient develops symptoms of the NSA, all antipsychotics should be immediately discontinued, including Ryspolept Konsta®.

Parkinson's disease and dementia with Levi bodies

The appointment of antipsychotics, including Ryspoleptus®Patients with Parkinson's disease or dementia with Levy bodies should be treated with caution, since in both groups of patients, the risk of neuroleptic malignant syndrome increased and sensitivity to antipsychotics increased (including blunting of pain sensitivity, confusion, postural instability with frequent falls and extrapyramidal symptoms). When taking risperidone, there may be a worsening of the course of Parkinson's disease.

Hypersensitivity reactions

Although the tolerability of oral forms of risperidone should be checked before the initiation of Rispolept® Constan® therapy, very rare cases of anaphylactic reactions are reported during post-marketing use in patients who previously tolerated oral risperidone forms.

In case of hypersensitivity reactions, it is necessary to stop using Rispolept® Constan®, to take the necessary supporting clinical measures and to monitor the condition of patients before the symptoms disappear.

Hyperglycemia and diabetes mellitus

When treating the drug Rispolept Konsta®, hyperglycemia, diabetes mellitus and exacerbation of already existing diabetes mellitus were observed. It is likely that the previous increase in body weight is also predisposing to this factor. It is very rare to have ketoacidosis and rarely - a diabetic coma. All patients need to be clinically monitored for symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness). Patients with diabetes should be monitored regularly for impaired glucose control.

Weight gain

In the treatment with Rispolept® Constan®, a significant increase in body weight was observed. It is necessary to monitor the body weight of patients.

Hyperprolactinemia

Hyperprolactinaemia is a common unwanted reaction in the treatment of risperidone.It is recommended to determine the concentration of prolactin in the blood in patients with signs of hyperprolactinaemia (for example, gynecomastia, menstrual irregularities, anovulation, impaired fertility, decreased libido, erectile dysfunction, galactorrhea).

Based on the results of studies on tissue cultures, it is suggested that cell growth in breast tumors can be stimulated by prolactin. Although clinical and epidemiological studies have not revealed a clear association between hyperprolactinaemia and antipsychotic medications, caution should be exercised in prescribing risperidone to patients with a history of history. The drug Rispolept® Constan® should be used with caution in patients with existing hyperprolactinemia and in patients with possible prolactin-mediated tumors.

Interval lengthening QT

Interval lengthening QT very rarely observed in the postmarketing period of follow-up. As with other antipsychotics, caution should be exercised when prescribing Rispolept Konsta® to patients with known cardiovascular diseases, lengthening the interval QT in a family history, bradycardia, electrolyte balance disorders (hypokalemia, hypomagnesemia), since this may increase the risk of arrhythmogenic effect; and when combined with drugs that extend the QT interval.

Convulsions

Rispolept Konsta® should be used with caution in patients with a history of seizures or with other medical conditions in which the convulsive threshold may be reduced.

Priapism

Priapism may occur with the use of risperidone due to alpha-adrenergic blocking effects.

Regulation of body temperature

Antipsychotic drugs attributed to such an undesirable effect as a violation of the ability of the body to regulate the temperature. Caution should be exercised when prescribing Rispolept Konsta® to patients with conditions that can contribute to increased central body temperature, such as intense physical activity, dehydration, exposure to high external temperatures, or simultaneous use of drugs with angiholinergic activity.

Venous thromboembolism

When using antipsychotic drugs, cases of venous thromboembolism were noted.Because antipsychotics often have a risk of developing venous thromboembolism, all possible risk factors should be identified before and during treatment with Rispolept Konsta®, and precautionary measures should be taken.

Intraoperative syndrome of sagging iris (ISDR)

ISDR was observed during the operative intervention for the presence of cataracts in patients receiving therapy with drugs with antagonist activity α₁adrenoreceptors, including the drug Rispolept Konsta®.

ISDR increases the risk of complications associated with the organ of vision, during and after an operation. The physician conducting such an operation should be informed in advance that the patient has taken or is currently taking drugs that have antagonist activity α₁adrenoreceptors. Potential benefit of discontinuing antagonist therapy α₁-adrenoceptors before surgical intervention is not established, and should be evaluated taking into account the risks associated with the abolition of antipsychotic drugs.

Antiemetic effect

In preclinical studies of risperidone, an antiemetic effect was observed. The appearance of this effect in a patient can mask the signs and symptoms of an overdose of certain drugs or such conditions as an intestinal obstruction, Reye's syndrome or a brain tumor.

Renal and liver failure

Despite the fact that Rispolept® Konsta® has not been studied in patients with renal or hepatic insufficiency, caution should be exercised when using the drug in such patient groups.

Care must be taken to avoid inadvertent administration of Rispolept® Constan® into the blood vessel.

Do not expose the product to temperatures above 25 ° C. In the absence of a refrigerator, the preparation Rispolept Konsta® before use can be stored at a temperature of no higher than 25 ° C for not more than 7 days.

After the suspension is prepared: the suspension is physically and chemically stable for 24 hours at a temperature of 25 ° C. From the microbiological point of view, it is desirable to use the suspension immediately after preparation. If the suspension is not used immediately after preparation, it can be stored for no more than 6 hours at a temperature of 25 ° C. Risperidone can reduce the rate of mental and physical reactions, and therefore patients should be advised to refrain from driving a vehicle and working with mechanisms.

Incompatible combinations

Rispeplet Konsta® can not be mixed or diluted with any other medicines and fluids other than the special solvent contained in the package.

Instructions for use

Important information

The use of Rispolept® Constan® requires strict adherence to the instructions for preparing the suspension in order to ensure accurate administration of the preparation and avoid possible errors.

Remove the Rispolept Konsta® package from the refrigerator and allow it to warm to room temperature for at least 30 minutes before preparing the suspension.

Do not heat it in any other way.

The components of this kit are specially developed for the use of the drug Rispolept Konsta®. To prepare a suspension from the Ripolepte Konsta® microgranules in the vial of the prolonged action, you can use only the solvent in the kit.

Do not replace the components in the packaging with any other products.

Do not store the suspension after cooking.

The drug should be administered immediately after the preparation of the suspension.

To ensure the use of a full dose of risperidone, the entire contents of the vial should be administered. The introduction of part of the contents of the vial can not ensure that the patient receives the correct dose of the drug.

Do not reuse: This device is intended for single use only. Any attempt at subsequent reuse may adversely affect the integrity of the device itself or lead to a deterioration in its operation.

Components of the kit

(see Figure 1)

1. Assemble the components.

Connect the needleless device to the bottle.

Remove the lid from the vial.

Remove the colored plastic lid from the vial.

Wipe the unopened vial with an alcoholic towel and allow to dry.

Do not remove the gray rubber stopper.

Prepare a needleless device.

Keep a sterile blister as shown. Pull back and remove the paper backing.

Do not remove the needleless device from the blister.

To prevent contamination, do not touch the sharp tip of the device.

Connect the needleless device to the bottle

Place the vial on a firm surface and hold the bottom of the vial. Place the needleless device on the bottle vertically so that the sharp tip is located in the center of the rubber stopper. Pushing down from above, push the sharp tip of the needleless device through the center of the rubber bottle stopper until the device is securely attached to the top of the bottle.

Do not connect the needleless device at an angle. The solvent may leak during transfusion into the vial.

Connect pre-filled syringe with a needleless device.

Remove the sterile blister.

Important! Remove the sterile bladder of the needleless device only when you are ready to remove the white cap from the syringe.

Keep the bottle upright to avoid leakage. While holding the bottom of the bottle, pull the blister to remove it.

Do not shake.

To prevent contamination, do not touch the luer tip.

Hold the syringe by the white collar.

Do not hold the syringe behind the glass base.

Remove the cap.

Hold the syringe by the white collar, break off the white cap.

Do not unscrew and cut off the white cap.

To prevent contamination, do not touch the tip of the syringe.

A broken cap can be thrown away.

Connect the syringe and the needleless device.

To prevent rotation during the connection, firmly hold the "skirt" of the needleless device.

While holding the syringe by the white collar, insert the tip of the syringe into the luer tip of the needleless device.

Do not hold the syringe behind the glass base. This can lead to the detachment of the white collar. Firmly screw the syringe to the needleless device clockwise.

Avoid twisting. This can lead to the exit of the syringe.

2. Dissolve the microgranules

Enter the solvent.

Enter the contents of the syringe with the solvent into the vial.

Important! Now the contents of the bottle will be under pressure. Hold the plunger of the syringe with your thumb.

Suspend microgranules in a solvent.

While holding the plunger of the syringe with your thumb, vigorously shake the contents of the vial for at least 10 seconds until a uniform suspension is formed.

After proper mixing, the suspension becomes homogeneous, thick, milky in color.

The microgranules can be seen in the liquid, but should not remain dry by the solvent of the dry microgranules.

Immediately proceed to the next step, since the suspension may be exfoliated.

Transfer the suspension to the syringe.

Turn the bottle upside down and SLOWLY draw the entire contents of the vial into the syringe.

Remove the needleless device.

While holding the syringe by the white collar, unscrew the syringe from the needleless device.

Separate part of the label from the vial along the perforation line and glue it to the syringe (for identification). Dispose of the bottle and needle-free device in accordance with local regulations for the disposal of this type of waste.

3. Attach the needle.

Choose the right needle.

Select the needle, depending on the injection site (gluteal or deltoid).

Attach the needle.

Open the blister pack and grasp the base of the needle, as shown in the figure.

Continuing to hold the syringe by the white collar, tighten the syringe tightly in the luer cannula of the needle guard by pressing and turning it clockwise.

To prevent contamination, do not touch the luer lock tip of the protective device.

Resuspend microgranules.

Completely remove the blister. Immediately prior to the administration of the drug, it is necessary to resuspend the microgranules, since after the suspension is prepared in the vial, some of the microgranules may settle. Vigorously shake the syringe.

Enter the drug.

Remove the transparent case from the needle

Pull the needle guard in the reverse direction from the syringe, as shown. While holding the syringe by the white collar, remove the transparent case from the needle. DO NOT bend the case; the connection of the luer tip can be violated.

Remove air bubbles.

Tap your finger lightly on the syringe so that the air bubbles in it are raised. Slightly pushing the piston upward, remove air bubbles from the syringe and needle, holding the syringe so that the needle points vertically upwards.

Enter the drug.

Immediately enter the entire contents of the syringe intramuscularly into the gluteus or deltoid muscle of the patient.

Injection into the gluteus muscle must be made in the upper outer quadrant of the gluteal region.

The suspension can not be administered intravenously.

Remove the needle into the protective device.

With one hand, place the protective device on a flat surface at an angle of 45 degrees.Rapidly move down until the needle enters the protection device.

Warning:

Do not use both hands.

Do not disassemble the needle guard.

Do not attempt to straighten the needle and do not touch the needle guard if the needle is bent or damaged.

Dispose of the needle properly.

Before you eject the needle, make sure that the needle is firmly attached to the needle protector.

Dispose of in accordance with local regulations for the disposal of this type of waste.

Also dispose of the unused needle in the kit.

Effect on the ability to drive transp. cf. and fur:Risperidone can reduce the rate of mental and physical reactions, and therefore patients should be advised to refrain from driving a car and working with mechanisms.

Form release / dosage:Powder for suspension for intramuscular administration of prolonged action, 25 mg, 37.5 mg and 50 mg.

Packaging:

The package includes:

- One vial of powder containing sustained release micro-granules of Ryspolept Konsta® at 25, 37.5 or 50 mg of risperidone. The color of the plug differs depending on the dosage of the drug: for 25 mg - pink, for 37.5 mg - green, for 50 mg - blue.

- One pre-filled syringe with 2 ml solvent.

- 1 needleless device for the preparation of West-Medimop Vial Adapter® suspension.

- 2 safety needles Terumo SurGuard®-3 (with protective device) for intramuscular injection. Needle length 25 mm is intended for insertion into the deltoid muscle, a needle 51 mm long is designed for insertion into the gluteus muscle.

The components are packaged in a contoured cell pack of a polyvinyl chloride film coated with a transparent polyethylene film.

One outline package together with the instruction for use is placed in a cardboard box.

Storage conditions:

Store at a temperature of 2 to 8 ° C, in a place protected from light.

Do not expose to temperatures above 25 ° C.

In the absence of a refrigerator, the drug can be stored at a temperature of no higher than 25 ° C for up to 7 days before use.

Shelf life:

Shelf life 3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N015674 / 01

Date of registration:26.05.2009 / 22.12.2015